dose-ranging study of rifaximin soluble solid dispersion (ssd) tablets for the prevention of complications of early decompensated liver cirrhosis

Conditions: Liver Cirrhosis

Summary: the primary objective of this study is to assess the efficacy of rifaximin ssd versus placebo in preventing complications of liver cirrhosis, such as all-cause mortality (death due to all causes) or hospitalization, in subjects with early decompensated liver cirrhosis. rifaximin, a non-systemic antibacterial agent, is currently marketed as a 550 mg tablet for the reduction in risk of recurrent overt hepatic encephalopathy, a complication of liver cirrhosis. the rifaximin ssd tablet was formulated to maximize the efficacy of rifaximin. subjects will receive 1 of 5 doses of rifaximin ssd tablets or placebo tablets every day for 24 weeks.


Eligibility criteria:
inclusion criteria: * diagnosis of liver cirrhosis and documented ascites. * model end stage liver disease (meld) score of at least 12, meld na of at least 12, or child-pugh b (score of 7 - 9). * if applicable, has a close family or other personal contacts who can provide continuing oversight to the patient and will be available to the patient during the conduct of the trial. * if female of childbearing potential, have a negative serum pregnancy test at study start and agree to use an acceptable method of contraception during the study. exclusion criteria: * history of a major psychiatric disorder including uncontrolled major depression or controlled or uncontrolled psychoses within the past 24 months prior to study start. * history of alcohol abuse or substance abuse within the past 3 months prior to study start. * documented cholestatic liver disease such as primary sclerosing cholangitis. * had prophylactic variceal banding within 2 weeks or is scheduled to undergo prophylactic banding during the study. * diagnosed with an infection for which the patient is currently taking oral or parenteral antibiotics. * significant hypovolemia, or any electrolyte abnormality that can affect mental function (eg, serum sodium \ 10 mg/dl). * severe hypokalemia, defined as serum potassium concentration \< 2.5 meq/l. * anemic, defined as hemoglobin concentration ≤ 8 g/dl. * renal insufficiency with a creatinine of ≥ 1.5 mg/dl. * presence of intestinal obstruction or inflammatory bowel disease. * uncontrolled type 1 or type 2 diabetes. * history of seizure disorders. * unstable cardiovascular or pulmonary disease, categorized by a worsening in the disease condition that requires a change in treatment or medical care within 30 days of study start. * active malignancy within the last 5 years (exceptions: basal cell carcinomas of the skin, or if female, in situ cervical carcinoma that has been surgically excised). * has hepatocellular carcinoma. * known human immunodeficiency virus, varicella, herpes zoster, or other severe viral infection within 6 weeks of study start. * positive stool test for yersinia enterocolitica, campylobacter jejuni, salmonella, shigella, ovum and parasites, and/or clostridium difficile (c. difficile); determined during the screening period prior to study start. * history of tuberculosis infection and/or has received treatment for a tuberculosis infection. * history of hypersensitivity to rifaximin, rifampin, rifamycin antimicrobial agents, or any of the components of rifaximin soluble solid dispersion. * used any investigational product or device, or participated in another research study within 30 days prior to study start.